Valerae O. Lewis

Patient survival after surgery for osseous metastases from renal cell carcinoma.

BACKGROUND Skeletal metastases from renal cell carcinoma are highly destructive vascular lesions. They pose unique surgical challenges due to the risk of life-threatening hemorrhage and resistance to other treatments. The goal of this retrospective study was to evaluate factors that may affect survival after surgical treatment of metastases of renal cell carcinoma. METHODS We performed a retrospective review of a series of 295 consecutive patients who had been treated for metastatic renal cell carcinoma at one institution between 1974 and 2004. There were 226 men and sixty-nine women. A total of 368 metastases of renal cell tumors to the extremities and pelvis were treated. The surgical procedures included curettage with cementing and/or internal fixation (214 tumors), en bloc resection (117), closed nailing (twenty-seven), amputation (four), and other measures (six). Overall survival was calculated with Kaplan-Meier analysis. The log-rank test was used to evaluate the effect of different variables on overall survival. RESULTS The overall patient survival rates at one and five years were 47% and 11%, respectively. The metastatic pattern had a significant effect on the survival rate (p < 0.0001): patients with a solitary bone metastasis had the most favorable overall survival rate. Patients with multiple bone-only metastases had a better survival rate than patients with pulmonary metastases (p = 0.009). A clear-cell histological subtype was also associated with better survival (p < 0.0001). The tumor grade did not predict survival (p = 0.17). Fifteen patients (5%) died within four weeks after surgery. The causes included acute pulmonary failure (seven patients), multiorgan failure (six), cerebrovascular accident (one), and hypercalcemia (one). There were no deaths attributable to intraoperative hemorrhage. DISCUSSION Survival beyond twelve months is possible for a substantial proportion of patients with metastatic renal cell carcinoma. Patients with a clear-cell histological subtype, bone-only metastases, and a solitary metastasis have superior survival rates. The presence of pulmonary metastases does not predict early death in a reliable manner, and some patients may survive for years with pulmonary and systemic disease. The data are important for surgeons to consider when choosing treatment for these patients. For example, local control of disease and implant stability are important issues for patients with a potential for a long duration of survival.

Radiotherapy in the management of giant cell tumor of bone

PURPOSE To evaluate the outcomes of patients with giant cell tumor of bone (GCTB) treated with radiotherapy (RT) with or without surgical resection. METHODS AND MATERIALS We performed a retrospective review of the records from 25 consecutive patients with pathologically confirmed GCTB who had undergone RT between 1956 and 2000. RESULTS Patients ranged in age from 11 to 69 years (median 32); 16 were female and 9 were male. The anatomic distribution of lesions was as follows: cervical spine, 3; temporal bone, 1; thoracic or lumbar spine, 9; sacrum, 8; ilium, 1, and humerus, radius, and thumb metacarpal, 1 each. Tumors ranged in size from 2 to 20 cm (median 9.5) at their maximal dimension. Thirteen patients had been referred for RT for primary GCTB and 12 had been referred with locally recurrent disease after having undergone one or more other treatments. Fourteen patients had undergone RT for gross disease, and the remaining 11 had been treated with RT after gross total resection. In 10 of these 11 patients, the treatment margins were positive or uncertain. Radiation doses ranged from 25 to 65 Gy (median 46). At a median follow-up of 8.8 years (range 0.67-34), 7 patients had developed isolated local recurrence, 2 had developed isolated distant recurrence, and 3 had developed both. The actuarial 5-year overall and disease-free survival rate was 91% and 58%, respectively, and the actuarial 5-year local control and distant metastasis-free survival rate was 62% and 81%, respectively. Univariate analysis suggested that treatment for recurrent disease correlated with a lower disease-free survival rate (83% vs. 33%, p = 0.06), distant metastasis-free survival rate (100% vs. 64%, p = 0.08), and local control rate (83% vs. 42%, p = 0.08) at 5 years. Of the 12 cases of recurrence, 7 were ultimately successfully treated with additional salvage therapy. In 4 of these patients, salvage therapy included interferon-alpha 2b. CONCLUSION RT should be considered an adjuvant to surgery or as alternative therapy in cases of GCTB that are unresectable or in which excision would result in substantial functional deficits. When RT is used as primary therapy, the rate of local control seems to be satisfactory. In heavily pretreated patients, however, RT delivered as it was in this series can result in poor local control, and alternative therapies should be considered.

18F-FDG PET/CT as an Indicator of Progression-Free and Overall Survival in Osteosarcoma

The aim of our study was to retrospectively evaluate whether maximum standardized uptake value (SUVmax), total lesion gylcolysis (TLG), or change therein using 18F-FDG PET/CT performed before and after initial chemotherapy were indicators of patient outcome. Methods: Thirty-one consecutive patients who underwent 18F-FDG PET/CT before and after chemotherapy, followed by tumor resection, were retrospectively reviewed. Univariate Cox regression was used to analyze for relationships between covariates of interest (SUVmax before and after chemotherapy, change in SUVmax, TLG before and after chemotherapy, change in TLG, and tumor necrosis) and progression-free and overall survival. Logistic regression was used to evaluate tumor necrosis. Results: High SUVmax before and after chemotherapy (P = 0.008 and P = 0.009, respectively) was associated with worse progression-free survival. The cut point for SUVmax before chemotherapy was greater than 15 g/mL* (P = 0.015), and after chemotherapy it was greater than 5 g/mL* (P = 0.006), as measured at our institution and using lean body mass. Increase in TLG after chemotherapy was associated with worse progression-free survival (P = 0.016). High SUVmax after chemotherapy was associated with poor overall survival (P = 0.035). The cut point was above the median of 3.3 g/mL* (P = 0.043). High TLG before chemotherapy was associated with poor overall survival (P = 0.021). Good overall and progression-free survival was associated with a tumor necrosis greater than 90% (P = 0.018 and 0.08, respectively). A tumor necrosis greater than 90% was most strongly associated with a decrease in SUVmax (P = 0.015). Conclusion: 18F-FDG PET/CT can be used as a prognostic indicator for progression-free survival, overall survival, and tumor necrosis in osteosarcoma.

Complications of combined modality treatment of primary lower extremity soft-tissue sarcomas

Correlations between various patient, tumor, and treatment characteristics and complications in patients undergoing combined modality treatment for primary lower extremity soft‐tissue sarcomas were investigated.

Long-term results of prospective trial of surgery alone with selective use of radiation for patients with T1 extremity and trunk soft tissue sarcomas

Objective:We conducted a prospective trial to define the local recurrence rates for selected patients with T1 soft tissue sarcomas (STS) treated by surgery alone. Summary Background Data:Retrospective data suggest that some patients with small STS can be safely treated by surgery alone. There are no defined criteria to select patients for such treatment. Methods:Patients with T1 primary STS were treated with function-preserving surgery and microscopic assessment of surgical margins. Postoperative external-beam radiation was employed selectively for patients with microscopically positive (R1) final surgical margins. Patients who underwent resection with microscopically negative (R0) final margins did not receive radiotherapy. Results:Eighty-eight eligible and evaluable patients were entered on this protocol between March 1996 and April 2002. Tumor sites included the extremities (n = 60), and trunk (n = 26). Fifty-one patients (58%) had high-grade STS; 60 (68%) had superficial (T1a) disease. Fourteen patients (16%) underwent R1 resection and were treated with postoperative radiation; 74 (84%) underwent R0 resection and were treated by surgery alone. The median follow-up was 75 months. Isolated local recurrences were observed in 11 patients (13%; 6 in R1 arm, 5 in R0 arm). In the R0 surgery-alone arm, the cumulative incidence rates of local recurrence at 5 and 10 years were 7.9% and 10.6%, respectively; and the 5- and 10-year sarcoma-specific death rates were 3.2% and 3.2%. Conclusion:Selected patients with primary T1 STS of the extremity and trunk can be treated by R0 surgery alone with acceptable local control and excellent long-term survival.

Imaging bone metastases in breast cancer: techniques and recommendations for diagnosis

Bone is the most common site of distant metastases from breast carcinoma. The presence of bone metastases affects a patients prognosis, quality of life, and the planning of their treatment. We discuss recent innovations in bone imaging and present algorithms, based on the strengths and weaknesses of each technique, to facilitate the most successful and cost-effective choice of imaging studies for the detection of osseous metastases. Skeletal scintigraphy (bone scan) is very sensitive in the detection of osseous metastases and is recommended as the first imaging study in patients who are asymptomatic. Radiographs are recommended for the assessment of abnormal radionuclide uptake or the risk of pathological fracture and as initial imaging studies in patients with bone pain. MRI or PET-CT can be considered for cases of abnormal radionuclide uptake that are not addressed by radiography. Osseous metastases can lead to emergent situations, such as spinal-cord compression or impending fracture of a weight-bearing bone, and imaging guidelines are essential for early detection and initiation of appropriate therapy. The imaging method used in non-emergent situations, such as assessment of the ribs, sternum, pelvis, hips, and joints, should be guided by the strengths and limitations of each technique.

Endoprosthetic and allograft-prosthetic composite reconstruction of the proximal femur for bone neoplasms

Reconstruction of the proximal femur after tumor resection can be achieved with either an endoprosthesis or an allograft-prosthetic composite. We compared the two modalities for complications, functional outcome, and construct survival. We retrospectively analyzed 52 patients with endoprostheses and 20 with allograft-prosthetic composite reconstructions between 1974 and 2002. Median followup was 146 months and 76 months, respectively. Both methods were associated with low rates of early complications. Infections occurred in two patients with endoprostheses and one patient with an allograft-prosthetic composite reconstruction. Aseptic loosening was the most common (10%) late complication for patients with endoprostheses. Nonunion was the most common (10%) complication for patients with allograft prosthetic composite reconstructions. All host-allograft junctions eventually healed after bone-grafting. The Musculo skeletal Tumor Society scores were similar for patients with endoprostheses (70%) and allograft-prosthetic composites (82%). The median hip abductor strength was greater for patients with allograft-prosthetic composite reconstructions (4.6 of 5) than for patients with endoprostheses (2.8 of 5). Kaplan-Meier survivorship of the implant was 86% for both groups at 10 years. The consistent restoration of abductor muscle strength combined with the low morbidity and high durability support the use of allograft-prosthetic composite reconstruction in patients with long life expectancy.Level of Evidence: Therapeutic study, Level IV (case series- no, or historical control group). See the Guidelines for Authors for a complete description of levels of evidence.

What's New in Musculoskeletal Oncology

This update will focus on the material in the field of musculoskeletal oncology that was published or presented over the past year. However, it should be noted that because musculoskeletal tumors are rare, the majority of the new articles and published research tends to be composed of retrospective or nonrandomized studies. ### Osteosarcoma The survival of patients with osteosarcoma has plateaued in the last ten years. In an attempt to improve the overall survival rate associated with the current chemotherapy agents, Wilkins et al. investigated a dose-intensified neoadjuvant intra-arterial chemotherapy regimen in a study of sixty-two pediatric patients with nonmetastatic osteosarcoma1. Intravenous doxorubicin and intra-arterial cisplatin were administered repetitively at three-week intervals until ≥90% reduction in tumor vasculature was seen with angiography. Chemotherapy was discontinued once one of four criteria was met: (1) ≥90% reduction in tumor vasculature, (2) a plateau in arteriographic change, (3) no response or progressive disease, or (4) completion of five neoadjuvant cycles. Patients received an average of four cycles of chemotherapy. There were no deaths due to chemotherapy toxicity, but six patients had development of cisplatin burns. Limb-salvage surgery was performed for 93.5% of the patients. The cisplatin burns were excised at the time of resection. Eighty-seven percent of the patients had a good histologic response (≥90% necrosis). The ten-year Kaplan-Meier estimate of the overall survival rate was 93.2%, and the event-free survival rate was 86.4%. The authors acknowledged that an explanation of the improved survival seen with this protocol is purely speculative. However, these results offer a new treatment regimen with the available chemotherapeutic agents. This is particularly promising given the results of both the Italian and Scandinavian Sarcoma Group and the Cooperative Osteosarcoma Study Group (COSS), which demonstrated that dose escalation or the addition of different chemotherapeutic agents does not correlate with better …

Treatment and prognosis of chondroblastoma

Chondroblastoma is an aggressive tumor of bone with the capacity for recurrence and metastasis. We sought to determine the prognostic factors that affect survival and local recurrence with particular emphasis on surgical technique and the anatomic constraints of the open physis. It was hypothesized that an open growth plate would impact the local recurrence rate negatively and be a primary determinant of treatment outcome. We retrospectively reviewed 82 consecutive patients treated at one institution. Intralesional treatment with meticulous curettage and bone graft resulted in local control in the majority of patients. Four local recurrences developed between 5 and 51 months. An open growth plate was not found to correlate with local recurrence. In most cases, the open physis did not considerably impact surgical technique. Although the median age of the patients was 16 years, the majority of patients had a closed or closing physis. Few patients had substantial growth remaining. A physeal-sparing operation was done in six patients, and no local recurrences were observed in this group. The factors that seemed to affect local recurrence included inadequate surgery and biologic aggressiveness of the tumor. Inadequate surgery was likely to be the cause of local recurrence in patients who presented after previous treatment elsewhere. Three patients who developed local recurrence manifested increased biologic aggressiveness of disease. These patients subsequently developed metastatic disease and malignant transformation of disease. All three patients died from their disease. Pelvic tumors tend to be biologically more aggressive and more apt to recur locally and metastasize to distant locations. Level of Evidence: Therapeutic Study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Phase I Trial of Preoperative Doxorubicin-Based Concurrent Chemoradiation and Surgical Resection for Localized Extremity and Body Wall Soft Tissue Sarcomas

PURPOSE The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with standard preoperative radiation for patients with localized, potentially resectable soft tissue sarcomas of the extremities or body wall. PATIENTS AND METHODS Twenty-seven patients with radiographically resectable intermediate- or high-grade soft tissue sarcomas were treated. Preoperative external-beam radiation was administered in 25 2-Gy fractions (total dose, 50 Gy). Concurrent continuous-infusion doxorubicin was administered by an initial bolus (4 mg/m(2)) and subsequent 4-day continuous infusion (12.5, 15.0, 17.5, or 20.0 mg/m(2)/wk). Radiographic restaging was performed 4 to 7 weeks after chemoradiation, and patients with localized disease underwent surgical resection. RESULTS Chemoradiation was completed as an outpatient procedure in 25 patients (93%). The maximum-tolerated dose of continuous-infusion doxorubicin combined with standard preoperative radiation was 17.5 mg/m(2)/wk; at this dose level, seven (30%) of 23 patients had grade 3 dermatologic toxicity. Macroscopically complete resection (R0 or R1) was performed in all 26 patients who underwent surgery. Among 22 patients who were treated with doxorubicin 17.5/mg/m(2)/wk with concurrent radiation and subsequent surgery, 11 patients (50%) had 90% or greater tumor necrosis, including two patients who had complete pathologic responses. CONCLUSION Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m(2)/wk. Pathologic response rates with this regimen are encouraging.